This project has centered around factors which regulate ketone body (acetoacetate and beta-hydroxybutyrate) metabolism. Studies will be continued to investigate the rates of production and utlization of ketone bodies in normal, obese and diabetic humans. Special emphasis will be given to the following aspects of ketone body metabolism: (1) the rates of production and utilization of ketone bodies and the rates of hepatic gluconeogenesis in diabetic patients during ketoacidosis, (2) aspects of acetone metabolism in diabetic patients in ketoacidosis, and (3) hepatic production rates of ketone bodies and glucose in normal and cirrhotic patients. Splanchnic arterio-hepatic venous differences for a variety of substrates associated with lipid and carbohydrate metabolism together with hepatic blood flow will be measured to quantitate production rates of ketone bodies and glucose. BIBLIOGRAPHIC REFERENCES: Owen, O.E., M.S. Patel, B.S.B. Block, T.H. Kreulen and F.A. Reichle. Gluconeogenesis in normal, cirrhotic and diabetic humans. Gluconeogenesis: Regulation in Mammalian Species. Edited by R.W. Hanson and M.A. Mehlman. John Wiley, New York, 1976. Owen, O.E. Interrelationships among key tissues in the utilization of metabolic intermediates. In Interrelationships Between Diabetes, Obesity and Atherosclerosis: Metabolic and Molecular Events in the Fate of Nutrients. Advances in Modern Nutrition, Volume II. Edited by R.J. Mahler and H.M. Katzen, John Wiley and Sons, New York, 1976.